Comparison between conjunctival autograft and post-op mitomycin c in patients of pterygium

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1 Comparison between conjunctival autograft and post-op mitomycin c in patients of pterygium Telgote V 1, Meena V 2, Singh A 3 1 Dr.Vandana Telgote, Associate Professor, Index Medical College & hospital and research Centre, Indore, 2 Dr Vandana Meena, Post graduate student, Department of Ophthalmolgy, Gandhi Medical college, Bhopal, MP, 3 Dr. Ankita Singh, PG Resident, Index Medical College & hospital and research Centre,Indore, MP, India Address for correspondence: Dr VandanaTelgote, vandanatelgote@gmail.com Abstract Introduction: Pterygium is one of the most common conjunctival diseases among ophthalmicpathologies, it is a fibro vascular encroachment of the conjunctival tissue on to the cornea, causing variable degree of ocular morbidity.the purpose of this study was to evaluate and compare recurrence rate in treating primary pterygium by two different techniques i.e. conjunctival autografting and intra-operative Mitomycin C (0.02%) with reference to recurrence and complication rate. Material and Methods: Present study was the prospective, comparative case study involving 80 eyes of 40 patients came in Index Medical College in OPD and Camp conducted in different rural areas. Patient were assigned to two groups (A and B) randomly. Group A underwent limbalconjuctivalautograft. Group B underwent pterygium excision augmented with postoperative topical mitomycin C application. Result: Out of the 80 patients maximum numbers of patients were in the age group from 41 to 50 years. there was a male preponderance in this study with 47 males (58.75%) as compared to 33 females (41.25%). It was found that recurrence of pterygium occurred in 2 (5%) out of 40 eyes treated with limbalconjuctivalautograft and 3 (7.5%) out of 40 eyes in whom pterygium excision was followed by postoperative mitomycin C. In Group B, 2 patients showed the sclera thinning while no complication found in Group A. There were no statistically significant differencebetween two groups. Conclusions: Conjunctivallimbalautograft and postoperative MMC (0.02%) are both safe and effective adjuncts to primary pterygium surgery. The main prejudices against auto- grafting are the expertise and time required for the procedure. The recent use of biologic adhesives to fixate the autograft in place may simplify the procedure. Age of the patients was strongly associated with recurrence regardless of which procedure was used. Key words: Pterygium, conjunctival autograft, intra-operative Mitomycin C. Introduction Pterygium is an excessive proliferation of fibrovascular tissue over the exposed ocular surface and frequently leads to almost irreversible visual loss. terygium is a common disorder in many parts of the world, with reported prevalence rateranging from 0.3 to 29%. Epidemiological studies suggest an association with chronic exposure to sunlight; with an increased geographical prevalence within a peri-equatorial pterygium belt of latitudes of 37 degrees north and south of the equator[1]. Reviewed: 15 th May 2015 Author Corrected: 25 th May 2015 Accepted for Publication: 04 th Jun 2015 Manuscript received: 14 th Jun 2015 Clinicallypterygium is a fibrovascular wing-shaped encroachment of conjunctiva onto the cornea[2]. Ultraviolet B light in solar radiation has been found to be the most significant environmental factorin pterygiumpathogenesis[1]. A recent study hassuggested that P-53 and human papilloma virus mayalso be implicated in pterygiumpathogenesis.ultraviolet radiation can cause mutation in genes such as the P-53 tumor suppressor gene, resulting in itsabnormal expression in pterygial epithelium. Thesefindings suggest that pterygium is not just adegenerative lesion, but could be a result ofuncontrolled cell proliferation[3]. Indications for surgery include visual Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 87 P a g e

2 impairment, cosmetic disfigurement, motility restriction, recurrentinflammation and interference with contact lens wear [4]. Surgical management includes simple excision with bare sclera technique,excision with adjunctive measures like intra-operativeand postoperative beta radiation, thiotepadrops,intra-operative mitomycin C and various techniques ofconjunctivalautografting. The reported recurrence rates of these techniques vary widely, from 5% forpterygium excision with conjunctivalautografting, to89% for simple excision[1,4]. Ablation with erbium oryag laser, and smoothening the corneal surface withexcimer[5]. laser has been tried but the results are notencouraging.mitomycin C is an antineoplasticantibioticalkylating agent isolated from fermentation filtrate ofstreptomyces caespitosus. It selectively inhibits DNAreplication by forming covalent linkages withguanosine residues in DNA, inhibits cellular RNA andprotein synthesis. Therefore, it prevents mitosisleading to cell death and interferes with collagensynthesis, thus preventing recurrence after pterygiumsurgery[6]. Although generally proven simple and effective, toxicity remains a concern. Complications reported with intra-operative or postoperative use ofmitomycin C are pain, iritis, secondary glaucoma,cataract, punctuate keratitis, chemosis, delayedconjunctival healing, conjunctival granuloma and scleral and corneal melting[7]. Many of these reportedserious complications involved use of highconcentrations ( %), prolonged postoperativetopical use and/or larger cumulative dosagesresulting from poor drug compliance[7,8]. Young AL et al have recommended intraoperativeuse [9]. The concentrations of intra-operativemitomycin C application used in most of the studiesrange from 0.01% to 0.04% with 0.02% applied form three months being the commonest dosage used [10]. Applying mitomycin C at the time of surgery providesclear advantage, such that the surgeon has controlover the medication delivery and, moreover, single,direct scleral bed application does not expose theentire ocular, nasal, nasolacrimal or oropharyngealsurfaces to the drug [11]. Our study was conductedto compare results of recurrence by excision with limbalconjunctivalautografts or postoperative topical Mitomycin C drops. Material and Methods Present study was the randomized, prospective, comparative case study involving 80 eyes of 40 patients came in Index Medical College in OPD and Camp conducted in different rural areas.the duration of the study was 2 years. The study was reviewed by the institutional review board. Each eligible patient provided informed consent prior to the enrolment in the study. Inclusion Criteria 1.All cases of pterygium attending the OPD including recurrent pterygium. 2. Patients came through Camp conducted in nearby rural areas. Exclusion Criteria Patients coming from far away places who were not able to come for regular follow up were excluded from this study. Patient with followings wereexcluded from the study. Recurrent Pterygium Previous Limbal surgery Ocular surface pathology Collagen vascular disorder Autoimmune diseases Infections Collection of Data- Detail ocular examination including visualacuity, refraction, IOP, extra- ocular movement,slit lamp biomicroscopy and fundoscopy wasdone before operative procedure. All 40 patientswere randomly assigned to two groups. Group A: Primary Pterygium excision with LCAG (limbal conjuctival autograft) Group-B: Primary Pterygium excision withmmc 0.02% Operative Procedure- Group-A (limbalconjuctivalautograft) Detachment of Pterygium head & dissectionof body from overlying conjunctiva Excision of sub conjunctivalpterygiumtissue Bare sclera gently cauterized Graft taken from supero-temporal aspect oflimbus, 1mm larger than the recipient bed Secured with 10.0 vicryl (episcleraly) In patients belonging to Group A excision of perygium was done followed by limbalconjuctivalautograft taken from upper temporal quadrant and sutured on the bare sclera using 6.0 vicrylsutures Patients were given gatifloxacin or moxifloxacin with dexamethasone eye drop 4 times a day for 2 weeks, then 3 times a day for 2 Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 88 P a g e

3 weeks, and then 2 times a day for 2 weeks. Gatifloxacin or moxifloxacin with dexamethasone ointment was applied at night for 6 weeks. The patient were followed after one week and then monthly for a year. Patients belonging to group B were treated with mitomycin C in a strength of 0.01 mg/ml in carboxy methyl cellulose. On first and second postoperative day patient were told to use either gatifloxacin or moxiflox- acin eye drops 6 times a day. From third to twenty first postoperative day patients were given mitomycin C drops 4 times a day and gatifloxacin (3 mg) with dexamethasone (1 mg) eyedrops 4 times a day. Patients were followed weekly for three weeks and then monthly for a period of one year. Best corrected visual acuity were noted on every visit. Patients were asked for any pain, photophobia, redness, lacrimation Group-B (MMC-0.02%) Intraoperative (MMC 0.02%) applied overbare sclera for 5 minutes Site of application was thoroughly irrigatedwith BSS solution. All patients were followed up for period of 18months (3, 6, 9, 12 and 18). Any recurrences orcomplications were recorded (Recurrencedefined as fibro vascular tissue invading the cornea >1.5mm). Statistical Analysis: Statistical analysis was done by calculation of range, median, mean, standard deviation, percentage, student t test. Statistical software: The statistical software SPSS 10.0 was used for the analysis of the data and Microsoft word and excel have been used to generate graphs, tables etc. Result The present study was conducted at the Index Medical College and Hospital & Research Centre, Indore, Madhya Pradesh over a period of 23 months (October 2011to September 2013). 80 eyes of 40 patients were enrolled in this study. Patients were assigned to two groups (A and B) randomly. Group A underwent limbalconjuctivalautograft, 40 patients. Group B underwent pterygium excision augmented with postoperative topical mitomycin C application included 40 patients. Out of the 80 patients maximum numbers of patients were in the age group from 41 to 50 years in which the youngest patient was 23 years of age and the oldest pa- tient was 70 years of age,there was a male preponderance in this study with 47 males (58.75%) as compared to 33 females (41.25%).65 pateints belong to rural areas and 15 from urban areas. There is no significant association between group A and B. Table 1: Demographic data of study participants Group A Group B Mean age(yrs) Age Sex Male Female Rural Urban Table 2: Recurrence rates PterygiumAutograft Pterygium Excision with Mitomycin C No. Of Eyes treated Recurrence No. % 2(5%) 3(7.5%) Table 3: Age of patients with recurrence Age of the patient Group A(ConjunctivalAutograft) Group B(Pterygium Excision with Mitomycin C) Less Than or Equal to 50 years 2(5%) 2(5%) Greater than 50 years 0 1(2.5%) Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 89 P a g e

4 In the present study it was found that recurrence of pterygium occurred in 2 (5%) out of 40 eyes treated with limbalconjuctivalautograft and 3 (7.5%) out of 40 eyes in whom pterygium excision was followed by postoperative mitomycin C. The present study shows that there were two recurrences in eyes with pterygium excision followed by conjunctivalautograft with age less than 50 years of age whereas in eyes with pterygium excision followed by mitomycin C there was one recurrence in patients less than 50 years and two recurrences in patients greater than 50 years of age. Table 4: Shows postoperative complications Type Of Complication Type A(ConjunctivalAutograft) Type B (Pterygium Excision followed with Mitomycin C) Scleral Thinning 0 2(5%) Above table shows that 2 cases (5%) of scleral thinning in eyes with pterygium excision followed by Mitomycin C while no complications had been seen in ConjunctivalAutograft. Discussion Pterygium is an excessive proliferation of fibrovascular tissue over the exposed ocular surface and frequently leads to almost irreversible visual loss. It is a worldwide disease which is particularly common in tropical and sub-tropical regions In the study conducted by AlemworkMeseretetal[12], prevalence of pterygium was more in middle and old age group. Our study shows that maximum number of patients were in the age group from 41 to 50 years in which the youngest patient was 23 years of age and the oldest was 70 years of age. So the present study agrees with the previous studies McCarty etal [13] found that the independent risk factors for pterygium were found to be age (OR=1.23, 95% CL=1.06, 1.44), male sex (OR=2.02, 95% CL=1.35, 3.03), rural residence (OR=5.28, 95% CL=3. 56, 7.84), and lifetime ocular sun exposure (OR=1.63, 95% CL=1.18, 2. 25). The attributable risk of sunlight and pterygium was 43.6% (95% CL=42.7, 44.6). The result was the same when ocular UV-B exposure was substituted in the model for broad band sun exposure.above studies observed that pterygium is more likely to occur in outdoor workers, and hence it is more common in men than in women. The present study shows a male preponderance with 47 males (58.75%) as compared to 33 females (41.25%). So the present study agrees with the previous studies. Jeanie et al[14] studies have indicated that pterygium occurs as a result of localized limbal dysfunction the success of conjunctivalautografting technique that include limbal tissue in the graft in treating primary & recurrent pterygia to provide for the Limbal Stem Cell deficiency has been highlighted. This study showed a higher prevalence in males. Previous studies showed similar results. In 1998 Lewallen et al[15] published report of a randomized trial of the conjunctivalautografting technique for pterygium removal. She documented a lower recurrence rate (21 %) in grafted cases compared with bare sclera technique (37 %). A recurrent pterygium can be associated with decreased visual acuity due to involvement of visual axis and/or irregular astigmatism, extraocular motility restriction and symblepharon formation [16]. Because of high recurrence rate the bare sclera excision alone proved unsatisfactory. Adjunctive treatment after bare sclera excision with beta irradiation reduced recurrence rate to as low as 0.5%-10% [17], but was associated with significant complications such as scleral necrosis. Sharma et al, 2003[18] found that Mitomycin-C is an alkylating antineoplasticagent which inhibits cellular division and replicationby inhibiting DNA systhesis. Intra operative MMC ispreferred and current regimen of 0.02% MMC for 5minutes has been found to be equally effective, simple,and has comparable recurrence rates. In conclusion,simple excision of pterygiumfollowed by MMC orlimbalconjunctival auto graft both yielded acceptableresults. Young et al (2004)[19] in their study found recurrence rate higher in group IIthan group I while in the present study it wasapporximately equal in both the groups. In contrastal et al[20] found thattwelve of 47 patients (25.5%) in the original MMC group and 2 of 29 patients (6.9%) in the LCAU group had recurrent pterygium (P = 0.021). The mean ECD was 2,39 2 ± 342 cells/mm(2) in the MMC group and 2,390 ± 388 cells/mm(2) in the LCAU group (P = 0.978). There was no significant Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 90 P a g e

5 difference in the ECD between the operated eyes and the fellow eyes in both groups (P = MMC, P = LCAU). No other significant ocular complications were observed in either group at the 10- year postoperative follow-up. NitinVichare et al[21] found that,the average surgical time taken was ± 4.96 min with suture group and ± 4.94 min with fibrin glue group. Pain and foreign body sensation was markedly less with fibrin glue group. At the end of final follow up at 6 months, 3 cases (10%) from suture group and 1 case (3.33%) from fibrin group had recurrence. Chen et al.[22] reported the mean time of recurrence varied from 3.7 to 4.8 months with only 6% of recurrences occurring after the sixth postoperative month. In the present study, cases where limbalconjuctivalautografting was done there was recurrence occurring in the first and third month whereas in cases where pterygium excision followed by mitomycin was done recurrence occurred in third, fourth and sixth month of follow up So the present study agrees with previous studies. Lam et al. [23] reported 2 cases (5.57%) of scleral thinning in the group in which they applied MMC. The present study shows, 2 cases (5%) of scleral thinning in eyes with pterygium excision followed by MMC which agrees with previous studies In the study conducted by Figueiredoet al.[24] patients with age less than 50 years had significantly more recur- rences. It has been suggested that lipoid degeneration in the cornea is an inhibiting factor to pterygium growth, based on observations that pterygium does not cross an arcussenilis to any great extent. The presence of increasing amounts of lipoid degeneration with age might explain in part, the strong association between age and recurrence. The present study shows that there were two recurrences in eyes withpterygium excision followed by conjunctivalautograft with age less than 50 years of age whereas in eyes with pterygium excision followed by mitomycin C there was one recurrence in patients less than 50 years and two recurrences in patients greater than 50 years of age which agrees with previous studies. Conclusion Simple excision of Pterygium followed by Limbalconjunctivalautografting (LCAG) and Mitomycin -C (MMC) 0.02%. Both yielded acceptable and comparable results &both are safe and effective adjuvant of Pterygium surgerylcag appeared to be technically difficult, time consuming and required skillful dissection and placement of graft, which is main limiting factor for successful grafting. Single intra operative MMC (0.02%) appear to be simple and equally effective and useful adjunctive therapy without serious complication. The choice of adjuvant should be carefully made by assessing the individual recurrence risk factors, and most importantly surgeon s expertise. More research needs to be done to delve into this seemingly innocuous pathology of conjunctiva to effectively manage the disease condition. Funding: Nil Conflict of interest: Nil Permission from IRB: Yes References 1. Taylor HR, West S, Muñoz B, Rosenthal FS, Bressler SB, Bressler NM. The long-term effects of visible light on the eye. Arch Ophthalmol Jan;110(1): Wong AK, Rao SK, Leug AT et al. Inferior limbalconjunctivalauto-graft transplantation for recurrent pterygium. Indian J Ophthalmol.2000; 48: 21-4.available on 3. Reisman D, McFadden JW, Lu G. Loss of heterozygosity and p53 expression in Pterygium. Cancer Lett Mar 31;206(1): Sebban A, Hirst LW. Pterygium recurrence rate at the Princess Alexandra Hospital. Aust N Z J Ophthalmol Aug;19(3): Koranyi G, Seregard S, Kopp ED. Cut and paste: a no suture, small incision approach to pterygium surgery. Br J Ophthalmol Jul;88(7): Nabawi KS, Ghonim MA, Ali MH. Evaluation of limbal conjunctival autograft and low-dose mitomycin C in the treatment of recurrent pterygium. Ophthalmic Surg Lasers Imaging May-Jun;34(3): Raiskup F, Solomon A, Landau D, Ilsar M, Frucht- Pery J. Mitomycin C for pterygium: long term evaluation. Br J Ophthalmol Nov;88(11): Wong VA, Law FC. Use of mitomycin C with conjunctival autograft in pterygium surgery in Asian- Canadians. Ophthalmology Aug;106(8): Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 91 P a g e

6 9. Young AL, Leung GY, Wong AK, Cheng LL, Lam DS. A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft after excision of primary pterygium. Br J Ophthalmol Aug;88(8): Oguz H, Basar E, Gurler B. Intraoperative application versus postoperative mitomycin C eye drops in pterygium surgery. Acta Ophthalmol Scand Apr;77(2): Manning CA, Kloess PM, Diaz MD, Yee RW. Intraoperative mitomycin in primary pterygium excision. A prospective, randomized trial. Ophthalmology May;104(5): MeseretA,Bejiga A, AyalewM.Prevalence of pterygium in rural community of Meskan District, Southern Ethiopia Ethiopian Journal of Health Development Vol. 22 (2) 2008 pp McCarty CA, Fu CL, Taylor HR. Epidemiology of pterygium in Victoria, Australia. Br J Ophthalmol Mar;84(3): Chui J, Coroneo MT, Tat LT, Crouch R, Wakefield D, Di Girolamo N. Ophthalmic pterygium: a stem cell disorder with premalignant features. Am J Pathol Feb;178(2): doi: /j.ajpath Lewallen S. A randomized trial of conjunctival autografting for pterygium in the tropics. Ophthalmology Nov;96(11): Shimazaki J, Shinozaki N, Tsubota K. Transplantation of amniotic membrane and limbal autograft for patients with recurrent pterygium associated with symblepharon. Br J Ophthalmol Mar;82(3): MacKenzie FD, Hirst LW, Kynaston B, Bain C. Recurrence rate and complications after beta irradiation... How to cite this article? for pterygia. Ophthalmology Dec;98(12): ; discussion Sharma A, Gupta A, Ram J, Gupta A. Low-dose intraoperative mitomycin-c versus conjunctival autograft in primary pterygium surgery: long term follow-up. Ophthalmic Surg Lasers Jul- Aug;31(4): Young AL, Leung GY, Wong AK, Cheng LL, Lam DS. A randomised trial comparing 0.02% mitomycin C and limbal conjunctival autograft after excision of primary pterygium. Br J Ophthalmol Aug;88(8): Young AL, Ho M, Jhanji V, Cheng LL. Ten-year results of a randomized controlled trial comparing 0.02% mitomycin C and limbal conjunctival autograft in pterygium surgery. Ophthalmology Dec;120(12): doi: /j.ophtha Epub 2013 Jul Vichare N, Choudhary T 2, Arora P 3. A comparison between fibrin sealant and sutures for attaching conjunctival autograft after pterygium excision. Med J Armed Forces India Apr;69(2): doi: /j.mjafi Epub 2012 Dec Chen P, Ariyasu R, Kaza V, et al. A Random- ized Trial Comparing Mitomycin C and ConjuctivalAutograft after Excision of Primary Pterygium, American Journal of Ophthalmology, Vol. 120, No. 2, 1995, pp Lam DS, Wong AK, Fan DS, Chew S, Kwok PS, Tso MO. Intraoperative mitomycin C to prevent recurrence of pterygium after excision: a 30-month follow-up study. Ophthalmology May;105(5):901-4; discussion Figueiredo RS, Cohen EJ, Gomes JA, Rapuano CJ, Laibson PR. Conjunctival autograft for pterygium surgery: how well does it prevent recurrence? Ophthalmic Surg Lasers Feb;28(2): Telgote V, Meena V, Singh A Comparison between conjunctival autograft and post-op mitomycin c in patients of pterygium. Biomed Rev: J Basic Appl Med Sci 2015;2(4): doi: /jbams.2015.i Biomedical Review: Journal of Basic and Applied Medical Sciences Available online at: 92 P a g e